Hematology & Transfusion International Journal

Autoimmune Hemolytic Anemia In Hodgkins Lymphoma:

A Case Report

Abstract Review Article

Auto-immune hemolytic anemia (AIHA) has an extensive differential diagnosis Volume 4 Issue 6 - 2017
though Hodgkins lymphoma (HL) is not always an obvious diagnosis. AIHA can
precede the diagnosis of HL for several years. In adults the association of AIHA and
HL is more frequent in advanced stages of HL. Warm immune hemolytic anemia is
mainly controlled with steroids and chemotherapy. We report a case of a patient
with positive direct Coombs test at the diagnosis of HL. This case reminds us that Pathology Department, Bhatia Hospital, India
Hodgkins lymphoma should be excluded in patients with hemolytic anemia or other
auto-immune (like) manifestations. *Corresponding author: Samir S Shah, Pathology
Department, 2nd Floor, Bhatia Hospital, Tukaram Jivaji Road,
Key words: Autoimmune haemolytic anemia; Hodgkins lymphoma; Warm immune Tardeo, Mumbai 400007, India, Tel: 022-66660643; Fax:
022-66660032; Email:

Received: January 12, 2017 | Published: June 19, 2017

Abbreviations: AIHA: Auto-Immune Hemolytic Anemia; HL:
Hodgkins Lymphoma; RS: Reed Sternberg; RA: Rheumatoid
Arthritis; SS: Sjgren Syndrome; SLE: Systemic Lupus
Erythematous; DLBCL: Diffuse Large B-Cell Lymphoma
Introduction
AIHA is a recognized complication of lympho -proliferative
disorders [1]. AIHA is rarely seen in HL patients with a reported
incidence of 0.2-4.2% [2]. Sporadic case reports and reviews have
shown that when AIHA occurs in HL patients it happens mostly
at stage III and IV of nodular sclerosis HL or mixed cellularity
HL [2]. HL is usually manifested as lymphadenopathy typically
in the cervical (70%), axillary (25%,), mediastinal areas (60%),
and in 16-34 % of the cases presents as nodal disease below the
diaphragm. HL presenting as AIHA has been reported in very
few case reports in literature. We hereby report a case HL who
presented as AIHA [1].
Case report
An 82 year old male patient with history of borderline
diabetes since 12 years presented with on an off fever, malaise,
generalized weakness, decreased appetite , weight loss, dizziness
and itching all over the body since 1 month. There was history of
hemiparesis, incontinence of urine and stool. On examination, his
vital parameters were stable. Systemic examination revealed mild
hepatomegaly and splenomegaly and bilateral basal crepitations
on auscultation of the chest. He was found to have fever of 40C
and pallor and right axillary lymphadenopathy which was non
tender and rubbery to feel. Laboratory investigations for liver
function tests revealed liver enzymes within normal ranges, with
unconjugated hyperbilirubinemia (with total bilirubin of 2.9 mg/
dl and indirect bilirubin of 1.6 mg/dl). LDH was 910 U/L. Iron
studies were within normal ranges.
The complete blood count revealed Hemoglobin of 5.6 gm/
dl, Hematocrit value 18.9%, MCV 113 fL, and MCH 33.5 pg and
reticulocyte count of 30%. WBC count was 20,770 cells/cumm with
1% Promyelocytes, 4% Myelocytes, 2% Metamyelocytes, 3% band
cells, 66 % Neutrophils, 4% Eosinophils,17% Lymphocytes, 3%
Monocytes. The peripheral smear examination showed moderate
anisocytosis and poikilocytosis with spherocytes, polychromatic
cells, Howell-Jolly bodies, Cabot rings, basophilic stippling and
70 nRBCs/100 WBCs and mild RBC agglutination. The corrected
WBC count was 12,217 cells/ cumm. Indirect and Direct Coombs
Test were strongly positive for IgG and C3. The reticulocyte count
was 30%. Hence, the diagnosis of AIHA was made. Serology for
Mycoplasma pneumoniae was negative. His chest X ray was
normal. Ultrasonography of the abdomen and pelvis revealed mild
hepatomegaly upto 15.3 cms with heterogeneous echotexture and
mild splenomegaly of 12.5 cms. There were few simple cortical
cysts in both the kidneys. Ultrasonography of right axilla showed
multiple enlarged lymph nodes with maintained fatty hilum and
increased vascularity .The largest lymph node was measuring 5.7
cms X 2.4 cms. There were no signs of necrosis or calcification.
The right axillary lymph node was biopsied and submitted for
histopathological examination. The biopsy (Figure 1) showed
polymorphous population of lymphocytes (Figure 2), plasma cells,
eosinophils and scattered mononuclear and binuclear variants of
Reed Sternberg (RS) cells. The immuno histochemistry on the
lymph node biopsy revealed all the RS like cells stained strongly
positively with CD 30 (Figure 3) (membranes and Golgi). Few RS
cells stain positively with CD 15 (Figure 4). These cells stained
negatively for CD45, CD 20 and Oct-2.

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Autoimmune Hemolytic Anemia In Hodgkins Lymphoma: A Case Report
Figure 1: Photomicrograph of bone marrow biopsy showing Reed-
Sternberg cells and its cellular environment.
Figure 2: Photomicrograph of Leishmans stained peripheral blood
smear showing spherocytes, RBC agglutination, nucleated RBCs,
neutrophil and lymphocyte.
Discussion
Patients affected by autoimmune diseases have demonstrated
an increased risk of developing lymphoid malignancies. Non-
Hodgkin lymphomas (NHL) have consistently been associated
with several autoimmune conditions. Such as, by way of example,
rheumatoid arthritis (RA), Sjgren syndrome (SS) and systemic
lupus erythematous (SLE). Similarly, even if based on fewer
studies, an increased risk of malignant lymphomas has also
been associated with celiac disease, dermatitis herpetiformis,
Hashimotos thyroiditis, and autoimmune hemolytic anemia.
Epidemiologic analysis by NHL subtype have shown that
diffuse large B-cell lymphoma (DLBCL) is more frequently
associated with RA and SS, while extra nodal marginal zone
lymphoma, in the respective target organs, is strongly associated
with SS (Theander et al, 2004) and Hashimotos thyroiditis.
Celiac disease is associated with a 520-fold increased risk of
Entheropathy-associated T-cell lymphoma of the small intestine
(EATL). Autoimmune conditions of the skin including psoriasis,
pemphigus and discoid lupus erythematous have an increased
risk of T-cell cutaneous lymphoma [4]. Hodgkins lymphoma has
also been associated with some autoimmune conditions, such as
RA, SLE and scleroderma (Table 1) [5].
AIHA is a recognized complication of lymphoproliferative
disorders, especially chronic lymphocytic leukemia. However HL
is rarely associated with AIHA. This association was first described
Citation: Shah SS, Khubchandani SR, Parikh RS, Vaswani LP (2017) Autoimmune Hemolytic Anemia In Hodgkins Lymphoma: A Case Report. Hematol
Transfus Int J 4(6): 00101. DOI: 10.15406/htij.2017.04.00101
Copyright:
2017 Shah et al. 2/3
Figure 3: Photomicrograph showing Reed-Sternberg cells staining
strongly positive for CD 30 (membranes and Golgi)
Figure 4:Photomicrograph showing Reed-Sternberg cells staining
strongly positive for CD 15.
by Eisner et al. [6]. The reported frequency of Coombs Positive
hemolytic anemia in adults with HL has ranged from 0.2% in a
large series of 492 from Europe [7] to 3 and 4 % in two American
studies [8]. When HL is accompanied by AIHA, the hemolysis is
usually detected at the time of diagnosis or a relapse [8]. Very
rarely has it been reported to precede the diagnosis of HD, in one
case by up to 7 years [9,10]. Immune mediated hemolytic anemia is
mostly seen in nodular sclerosing subtype and in mixed cellularity
subtypes [3]. In majority of these patients, AIHA is associated
with clinical or pathological evidence of stage III or stage IV
disease. The exact mechanism of AIHA in HL is still unclear [1].
However it may be postulated that the auto antibodies are directly
produced by tumor cells or are related to an immune regulatory
phenomenon. It is possible that there is an autoimmune process
at the early stages of HL in which antibodies are produced against
the tumor as well as the red blood cells as a Para- neoplastic
phenomenon. The antibodies prevent the growth of the tumor
at least initially, which later escapes the anti- tumor effect of the
antibodies and finally manifests as HL [11]. Patients with HL
are known to have an impaired cell mediated immune response
due to increase in number as well as function of T lymphocytes.
Decreased number of cytotoxic T cells could lead to excessive
autoantibody production. This appears to be partly due to hyper
activation of B-cells [4]. The other autoimmune manifestations
may include the development of neurological disorders, including
neuropathies, glomerulonephritis, vasculitis and rarely, arthritis.
 Copyright:
Autoimmune Hemolytic Anemia In Hodgkins Lymphoma: A Case Report 2017 Shah et al. 3/3

Taken together these manifestations highlight the prominent with systemic chemotherapy. Our patient presented with severe
relationship between immune dysfunction and HD [12]. AIHA for which no etiology was found at initial presentation.
This report illustrates that a patient with AIHA should be
Table 1: Most frequent histological subtypes associated with singular
autoimmune entities and known risk factors [5]. carefully investigated particularly in treatment resistant cases for
manifestations of HL.
Autoimmune Most frequent
entities subtype
Risk factors Acknowledgement
The authors have no conflicts of interests, including specific
Rheumatoid Diffuse large B- cell High inflammatory financial interests, relationships and / or affiliations, relevant to
arthritis lymphoma activity , Male gender
the subject matter or materials included.

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AIHA is a recognized complication of lymphoproliferative
disorders, especially chronic lymphocytic leukemia. HL however
is rarely associated with AIHA but should be considered in
the presence of warm agglutinin hemolytic anemia. Although
the initial treatment of AIHA is steroids, immune haemolysis
associated with Hodgkins disease requires definitive treatment
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Citation: Shah SS, Khubchandani SR, Parikh RS, Vaswani LP (2017) Autoimmune Hemolytic Anemia In Hodgkins Lymphoma: A Case Report. Hematol
Transfus Int J 4(6): 00101. DOI: 10.15406/htij.2017.04.00101